The present invention relates to a mass spectrometry apparatus. More particularly the present invention relates to a mass spectrometry apparatus suitable for ionizing a sample in a liquid and introducing the resultant ions into a mass spectrometer.
At present, apparatuses using liquid chromatography/mass spectrometry (which will hereinafter be abbreviated as LC/MS) and capillary electrophoresis/mass spectrometry (which will hereinafter be abbreviated as CE/MS) are considered to be new promising separation analyzers for Volatile or nonvolatile compounds. FIG. 9 is a construction diagram of a conventional LC/MS apparatus. A LC/MS apparatus is an analyzer using a mass spectrometer for a liquid chromatograph detector. The apparatus of FIG. 9 is a conventional example using a magnetic sector type mass spectrometer as a mass spectrometer, in which other types of mass spectrometers, such as a quadruple mass spectrometer, an ion trap mass spectrometer, an ion cyclotron resonance mass spectrometer and a time of flight mass spectrometer can also be used. In an analyzer using LC/MS, measurement is conducted generally as follows. A sample in a liquid separated by and sent out from a liquid chromatograph 1 is introduced sequentially into an ion source 22. The sample is ionized in this part to turn it into ions thereof. The ions thus generated are introduced into a magnetic sector type mass spectrometer consisting of an electric field 24 and a magnetic field 25 which are evacuated by vacuum pumps 23a, 23b, 23c, 23d, and are then mass separated. The mass separated ions are detected by a detector 26. A detected signal is amplified by an amplifier 27 and then sent to a data processor 28, in which it is subjected to mass spectrometry.
In the apparatus using LC/MS, the liquid chromatograph handles a sample in a liquid, while the mass spectrometer handles ions in a vacuum. Therefore, the important points of the development of an apparatus using LC/MS reside in techniques for ionizing a sample in a solution eluting from the liquid chromatograph 1. Some ionization methods have heretofore been proposed. A typical ionization method is an electrospray method disclosed in Japanese Patent Laid-Open Nos. 41747/1985 and 41748/1985. In the electrospray method, an apparatus shown in FIG. 10 is used. In this apparatus, a sample solution forced out by a suitable pump is introduced into a capillary 4 in an electrospray ion source 3. Usually, this capillary consists of a metal. When several kV of voltage is applied between this capillary 4 and a counter electrode 60, the sample solution becomes conical at a free end of the capillary, and an electrostatic atomization phenomenon in which a large number of fine droplets are formed at a free end of the cone.
A reference numeral 61 denotes a gas introduction port. When a gas, such as dry nitrogen is introduced into this port, the fine droplets are gasified with the gas blown out from a hole made in the counterelectrode 60, and ions occur in this process. These ions enter a differential pumping region 11 enclosed with a nozzle 7 and a skimmer 9 and evacuated by a roughing vacuum pump, and are introduced into a mass spectrometer under high vacuum through the skimmer 9, in which spectrometer the ions are subjected to mass spectrometry.
When the electrospray method is applied to a magnetic sector type mass spectrometer in which an accelerating voltage of not less than 1.5 kV is used, the following problems arise. The ions, fine droplets and neutral molecules generated by the electrospray method pass through the skimmer 9 in the differential pumping region 11 (pressure is not less than 10.sup.-3 Torr), and are blown into a vacuum (pressure is not more than 10.sup.-3 Torr) in which the mass spectrometer is provided. FIG. 11 shows the behavior of the ions 29 and neutral molecules 30 taken into the differential pumping region. When the ions 29 are accelerated by a high accelerating voltage immediately after they have passed through the skimmer, they have high kinetic energy and collide with residual neutral molecules 30. During this time, the kinetic energy of the ions is converted into internal energy. When the converted internal energy is large with the ions consisting of organic molecules, the decomposition of the organic molecules occur. Especially, when the ions generated consist of multiply charged ions (ions having a large number of electric charges), they give rise to problems. For example, even when the same ion accelerating voltage is used, the quantity of the kinetic energy obtained by ions of charge-state of +3 becomes thrice that of the kinetic energy obtained by ions of charge-state of +1. Accordingly, the ions of charge-stage of +3 collide with neutral molecules with large energy, and the ions become ready to be decomposed. In fact, when a quadruple mass spectrometer in which a low ion accelerating voltage (for example, 10 V) is used is employed, ions of charge-stage of +3 in which three protons are deposited on bradykinin molecules, ions of a kind of peptide by the electrospray method are clearly observed. However, when these ions of charge-state of +3 are accelerated at once at 4000 V and introduced into a magnetic sector type mass spectrometer in which an ion accelerating voltage (for example, 4000 V) is high, they are decomposed at a stroke to ions which occur when the bradykinin is decomposed. Therefore, when the ion accelerating voltage is high, it is difficult to determine the molecular weight of the bradykinin molecules.
A method of preventing such a phenomenon in which the ions are decomposed was made public in the American Academic Circle of Mass Spectrometry (The 39th ASMS Conference on Mass Spectrometry and Allied Topics, p. 244, 1991). FIG. 12 shows voltages applied to the electrospray ion source and differential pumping region used in this method. In addition to the first differential pumping region 51 (pressure is not less than 10.sup.-3 Torr) evacuated by a roughing pump, one more differential pumping region, i.e. a second differential pumping region 52 (pressure is the level of 10.sup.-4 Torr) evacuated by a turbomolecular pump is provided.
In the first differential pumping region 51, the number of neutral molecules is large, so that the ions collide with the neutral molecules repeatedly many times. The acceleration of ions in the first differential pumping region is substantially negligible. Therefore, the ions are substantially accelerated by a difference in voltage between a skimmer 9b and a slit 53. Accordingly, the ion accelerating voltage is equal to a difference in voltage between the skimmer 9b and slit 53.
In a method using two such differential pumping regions with an ion accelerating voltage of, for example, 4000 V employed, a voltage of 200 V is applied between skimmers 9b, 9c, and an ion accelerating voltage in the second differential pumping region 52 in which the vacuum is in the level of 10.sup.4 Torr is set lower. The remaining 3800 V is applied between the skimmer 9c and slit 53 so as to accelerate the ions in a region (pressure is not more than 10.sup.-6 Torr) ahead of the skimmer 9c in which the collision of ions with neutral molecules less frequently occurs, whereby the decomposition of the ions ascribed to the collision of ions with neutral molecules is minimized.
In a conventional method using two differential pumping regions, it is necessary to provide a differential pumping region. This causes the apparatus to be enlarged and complicated. There is also a problem that the ion transmission efficiency decreases greatly in the differential pumping region with the sensitivity of the apparatus thereby lowered.